Oncogenic activation has proven to be a valuable genetic marker for the identification of novel vertebrate genes [Varmus, H., Science 240, 1427-1435 (1988)]. The ras gene family, certain tyrosine protein kinases (src gene family, abl, trk, met, ret) and transcription factors (los, jun, erbA) are just some of the best known examples. Although the precise function of these genes remains to be elucidated, their capacity to induce neoplasia strongly suggests that they play critical roles in the control of signal transduction processes [Bishop, J. M., Science 235, 305-311 ( 1987 )].
The property of oncogenic activation has been used to isolate a number of novel human genes, one of which (vav) has been recently characterized at the molecular level. The ray gene was first identified when it became activated as an oncogene by a fortuitous rearrangement during the course of gene transfer assays [Katzav, S. et al., EMBO J. 8, 2283-2290 (1989)]. Molecular characterization of the human vav oncogene revealed a molecule capable of coding for a 797 amino acid polypeptide whose amino-terminus had been replaced by spurious sequences derived from the bacterial Tn5 gene used to confer G418 resistance to the transfected cells [Katzav, S. et al., supra]. The rest of the vav oncogene product contains a series of structural motifs reminiscent of those found in certain transcription factors, including a highly acidic amino-terminal region and a cystein-rich domain that depicts two putative metal binding structures [Johnson, P. F. et al., Annu. Rev. Blochem. 58, 799-839 (1989)].
The most intriguing feature of the vav gene is its pattern of expression. Analysis of ray gene transcripts in a series of human cell lines indicated that the vav gene is specifically expressed in cells of hematopoietic origin [Katzav, S. et al., supra]. No vav gene expression could be observed in either epithelial, mesenchymal or neuroectodermal cells. Interestingly, lymphoid, myeloid and erythroid cell lines contained comparable levels of vav gene transcripts. Similar results were obtained when normal human cells were examined, including B and T lymphocytes, macrophages and platelets [Katzav, S. et al., supra]. These observations suggest that the vav gene may play a basic role in hematopoiesis that is not influenced by differentiation programs.
It would be useful to isolate oncogenes from other mammalian species related to the human vav oncogene in order to more easily study the role of this protein in oncogenesis.